Eleni Efstathiou, MD, PhD, spoke about the positive results seen in the phase 3 MAGNITUDE trial in patients with metastatic castration-resistant prostate cancer harboring homologous recombination repair gene alterations who were treated with a niraparib-containing regimen.
In an interview with CancerNetwork® during the 2022 Genitourinary Cancer Symposium, Eleni Efstathiou, MD, PhD, section chief of Genitourinary Medical Oncology at Houston Methodist Oncology Partners in Texas, spoke about the results of the phase 3 MAGNITUDE trial (NCT03748641) in which patients with metastatic castration-resistant prostate cancer who had homologous recombination repair gene alterations were treated with niraparib (Zejula) or placebo, both plus abiraterone (Zytiga) acetate and prednisone, as a first-line therapy.
The primary end point was radiographic progression-free survival by blinded independent review. The secondary end points included overall survival, time to cytotoxic chemotherapy, time to symptomatic progression, and other very important considerations. The results of this study are positive for the primary end point [showing] a benefit for the combination of niraparib plus abiraterone acetate in combination with low-dose steroids such as prednisone [HR, 0.73; 95% CI, 0.56-0.96; P = .0217].
The study included a subset of patients who are DNA damage response gene mutation negative. The big question is, why was that cohort found to be negative for benefit? The way the study was designed [involved] an interim analysis that happened upon inclusion of a set number of patients, about 200. In that initial analysis, there was a futility clause that looked to see if there was any benefit [with active therapy], and no benefit was found. It was considered inappropriate or to have no value for adding more patients to the cohort that did not harbor deleterious mutations. If we are to go back and look at the design of the study, it is very important to take into consideration that that futility clause was there to keep us in check. That may account for the fact that we did not go on to include more patients that may have shown a small benefit. We always need to keep in mind that when we’re looking at in these phase 3 studies, it is not just about a statistical significance. It is also clinical significance that is in the back of our mind when we’re designing such studies.
Chi K, Rathkopf D, Smith M, et al. Phase 3 MAGNITUDE study: first results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration- resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. J Clin Oncol. 2022; 40(suppl_6):12. doi: 10.1200/JCO.2022.40.6_suppl.012